Compounds having opiate activity and useful as analgesic agents have been isolated from extracts of animal tissue and their amino acid sequences determined, in particularly the pentapeptides methionine enkephalin (Met-Ek) and leucine enkephalin (Leu-Ek) [Hughes, J. et al., Nature 258, 577 (1975)]. Both Met-Ek and Leu-Ek from mammalian brain have been shown to produce a weak and short term analgesia following intracerebra-ventricular or intravenous administration to mice [Buscher, H. H., et al., Nature 261, 423 (1976)] and rats [Belluggi, J. D., et al., Nature 260, 625, (1976)], and have been assumed to arise biologically from the larger enkephalin containing peptide, .beta.-endorphin.
Immunocytochemical observations of the adrenal medulla [Schultzberg, M. et al., Neuroscience 3, 1169 (1978)] have shown the presence of relatively large amounts of material immunoreactive with enkephalin peptides. Other reports of enkephalin peptides isolated and characterized from bovine adrenal medualla have been made, i.e. Lewis, R. V., et al., in Biochem, Biophys. Res. Commun. 89, 822, (1979); in Neural Peptides and Neural Communication (Costa, E., and Trabucchi, M., eds) pp 167-179, Raven Press, New York; and in Science 208, 1459 (1980); Kumura, S., et al., Proc. Nat. Acad. Sci. U.S.A. 77, 1681-1685 (1980).
Kensaku, et al., Biochem. Biophys. Res. Comm. 95, 1482-1488 (1980) reported the isolation from bovine adrenal medulla of a dodecapeptide having the following sequence of amino acids: